Effects of audio and visual distraction on patients’ vital signs and tolerance during esophagogastroduodenoscopy: a randomized controlled trial

Background Esophagogastroduodenoscopy (EGD) provides an indispensable and unambiguous inspection allowing the discovery upper gastrointestinal lesions. However, many patients are anxious about undergoing EGD. Few studies have investigated the influence on patients’ vital signs and tolerance during EGD using subjective and objective assessments. This study was a prospective randomized controlled study that investigated the influence of audio and visual distraction on EGD. Methods We randomly divided 289 subjects who underwent EGD into 4 groups (control group, audio group, visual group, combination group) and examined their vital signs, heart rate variability (HRV), psychological items, and acceptance of distraction. Results Pulse rate (PR) at post-distraction and post-EGD in the 3 distraction groups were significantly lower than those of control group (p <  0.001 and p <  0.01, respectively). Blood pressure (BP) during and post-EGD was significantly higher than that at pre-EGD in control group (p <  0.05), but no significant elevation of BP was observed during the latter half of EGD and post-EGD in the 3 distraction groups. BP at post-distraction improved significantly compared to pre-distraction in the 3 distraction groups (p <  0.05). There was a significant difference in the low-frequency (LF) power/ high-frequency (HF) power at post-distraction and post-EGD among the 4 groups (p <  0.001 and p <  0.001, respectively). The LF power/HF power at post-distraction and post-EGD in the 3 distraction groups was significantly lower than that in control group (p <  0.05). Several items of profile of mood states (POMS) and the impression of EGD at post-distraction improved significantly compared to those at pre-distraction among the 3 distraction groups (p <  0.05). Visual analog scale (VAS) of willingness for the next use of distraction in the 3 distraction groups was excellent because VAS was more than 70. Conclusions Distractions effectively improved psychological factors, vital signs and some of HRV at pre and post-EGD. Distractions may suppress BP elevation during the latter half of EGD and lead to stability of HRV on EGD. Trial registration This prospective trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000029637. Registered on 20 October 2017.


Background
Medical opportunities for the use of esophagogastroduodenoscopy (EGD) for the diagnosis of and therapy for etiology of gastrointestinal complaints and upper gastrointestinal cancer have increased. The development of smaller endoscope diameters reduced the unpleasant feeling and pain during EGD, but some person avoid undergoing EGD because of strong anxiety prior to the procedure [1][2][3]. Sedation increases the success rate of endoscopy and patient satisfaction during the endoscopic procedure [4][5][6][7][8], but sedation may increase the likelihood of complications, such as hypotension and respiratory depression [9][10][11][12][13]. Therefore, methods to improve patient anxiety during endoscopic examinations without sedation were examined. Several noninvasive intervention techniques, such as distraction using audio, visual, and olfactory stimulation, were introduced to decrease pain and anxiety during endoscopic examinations. Listening to music or watching images during various endoscopic procedures was an effective distraction in several reports, but most these reports used subjective assessments, such as pain, anxiety, and satisfaction [1,[14][15][16]. Few reports investigated the efficacy of the distraction of listening to music or watching images during EGD using a combination of subjective and objective assessments, including cardiovascular responses, heart rate variability (HRV), and a psychological questionnaire. We performed a prospective single-blind randomized controlled trial to assess the influence of distractions, such as audio and visual stimuli, during EGD.

Study design
This study protocol is included in additional Figure 1. This study was designed as a prospective, single-blinded randomized controlled trial, and it was performed at Shikoku Central Hospital of the Mutual Aid Association of Public School teachers. The Ethics Committee in Shikoku Central Hospital of the Mutual Aid Association of Public School teachers approved the study protocol, which was registered in the University Hospital Medical Information Network (UMIN Clinical Trials Registry, number UMIN000029637). Figure 1 shows a flow diagram of the enrollment and procedures of this study. A total of 360 subjects were scheduled to receive EGD at a regular health check-up at our hospital participated in this study between October 2017 and March 2018. The study design was explained, and all subjects provided written informed consent. Seventy-one subjects were excluded from the study if they met any of the following criteria: (1) current medication use; (2) a history of severe heart failure, renal failure, hepatic failure, or chronic obstructive pulmonary disease; (3) previous abdominal surgery, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD); (4) audio or visual disability; (5) previous experience of bad feelings from audio or visual stimuli; (6) a history of anxiety or psychiatric disorders; (7) pregnant or a possibility of pregnancy; and (8) receiving a diagnosis of gastrointestinal cancer or required biopsy. Subjects presented to the endoscopy floor in the morning after a longer than 12-h fasting period. Subjects who was divided into two categories those underwent EGD for the first time and those experienced EGD previously and each subject was randomly divided into 4 groups using a sealed opaque numbered envelope method by the endoscopy nurse who assisted at EGD. All subjects sat on a sofa and rested quietly for 5 min in a private room near the endoscopy room. Subjects in control group continued to sit on the sofa and rest quietly for 10 min prior to EGD. Subjects in audio group sat on the sofa and listened to music for 10 min. Subjects in visual group sat on the sofa and watched a silent natural image for 10 min. Subjects in combination group sat on the sofa and watched a natural image while listening to music for 10 min. The study used healing music, such as country and classical music, based on the tone of a music box, which was chosen as good by 20 volunteers in a pre-meeting prior to the start of this study. The moving images used in this study were various natural images, including a mountain, forest, river, waterfall, lake, and sunset. Music and natural images were delivered using a wall-type Hivision liquid crystal television (TH-42AS650; Panasonic Corporation, Osaka, Japan). Pharyngeal anesthesia with lidocaine pump spray (Xylocaine Pump Spray 8%; Astra-Zeneca, Osaka, Japan) without any sedative agents was applied, and 5 endoscopy specialists with greater than 5 years of experience in endoscopy performed a standard EGD, including observations of the esophagus, stomach, and duodenum, using a conventional single channel endoscope (GIF-H260; Olympus, Tokyo, Japan) without knowledge of the group of the subject. The profile of mood states (POMS) and the visual analog scale (VAS) of impressions for EGD were performed at pre-and post-distraction. VAS of the acceptance of distraction was performed after EGD.

Measurement of vital signs
Pulse rate (PR) and blood pressure (BP) were measured in the right upper arm, and peripheral blood oxygen saturation (SpO 2 ) was measured at the left finger using a monitor unit (BSM-7100 Life Scope; NIHON KOHDEN CORPORATION, Tokyo, Japan). These parameters were measured 5 and 15 min after sitting on the sofa, during EGD, and 5 min after EGD procedure. Parameters during EGD were measured just after insertion of the endoscope through the esophagogastric junction (approximately 2 min from the start of EGD) and just after moving the endoscope from the stomach to the esophagogastric junction (approximately 5-7 min from the start of EGD).

Assessment of HRV
We assessed autonomic nervous function from pre-EGD to post-EGD using power spectral analysis (PSA). HRV was measured using a Heart Rhythm Scanner (HRV analysis system from Biocom Technologies, Ark Trading Pacific, Inc.) equipped with software that performed algorithms for short-term HRV analysis. A Biocom HRS-08 Bluetooth Wireless Pulse Wave Sensor photoplethysmography monitor was used in this study, and it was clipped to the right earlobe. Data of the average R-R intervals for 5 min were subjected to PSA using the software of the HRV analysis system. The amplitudes of the low-frequency (LF) range (LF, 0.04-0.15 Hz) and highfrequency (HF) range (HF, 0.15-0.40 Hz) were analyzed using complex demodulation. These LF and HF values were designated as the LF power and HF power, respectively. HF power is fluctuation in the heart rate caused by respiration, which is mediated by cardiac parasympathetic nervous activity [17,18]. The ratio of LF power to HF power is an index of sympathetic nervous activity [19][20][21][22]. The HF power data were converted to a logarithmic scale to analyze using linear regression in the present study.

Psychological assessment and acceptance of distraction
We used the POMS2 questionnaire for psychological assessments between pre-and post-distraction because POMS is a self-report measure that quickly assesses transient, fluctuating feelings and enduring affective states [23,24]. The POMS2 is composed of 35 items and 8 subscale scores. We also used the VAS, which consists of a 100-mm horizontal line scored from 0 to 100 to rate the degrees of strain, anxiety, and fear of EGD. All subjects answered the POMS and provided their impressions of EGD immediately after sitting on the sofa and 15 min after sitting on the sofa, but prior to EGD. After EGD, subject used the VAS to rate their degrees of satisfaction, usefulness, and willingness to assess the subject's acceptance of distraction.

Outcomes
The primary outcome measures were psychological factors including POMS and impression for EGD at postdistraction and acceptance of distraction including degrees of satisfaction, usefulness, and willingness for the next use at post EGD. The secondary outcome measures were vital signs, HRV at post-distraction, during EGD, and at post-EGD. Vital signs and HRV were measured at pre-EGD (5 min after sitting on the sofa), pre-EGD (15 min after sitting on the sofa), during the early and the latter half of EGD, and 5 min after the end of EGD.

Statistical analysis
We assumed that the appropriate sample size for the randomized subjects was over 180 subjects based on the requirement of a significant difference between 4 groups with a significance level of 0.05, power of 80%, and, effect size of 0.25. Additionally, the rate of subjects who fill exclusion criteria or who received a diagnosis of gastrointestinal cancer or a biopsy was 30-40% by referring to our previous prospective randomized trial on endoscopy. Therefore, the planned required number of subject who receive EGD was over 300. Quantitative data, including subject characteristics, vital signs, POMS score, and VAS scores of impressions for EGD and acceptance of distraction, are expressed as the means ± standard deviation (SD). Parameters of autonomic nervous function are expressed as the means ± standard error of the mean (SEM). All significant differences at a P value less than 0.05 were considered

Results
Baseline characteristics of subjects Table 1 shows the baseline characteristics in the 4 groups. There was no significant difference in age, gender, smoking, drinking, experience or duration of EGD, POMS, and the impression for EGD among the 4 groups. Figure 2 shows the changes in PR from pre-EGD to post-EGD in the 4 groups. PRs during the early and the latter half of EGD, and 5 min after the end of EGD were significantly higher than pre-EGD (5 min after sitting on the sofa) in control group and audio group (p < 0.001, p < 0.001, and p < 0.05). PRs during the early and the latter half of EGD were significantly higher than pre-EGD (5 min after sitting on the sofa) in visual group (p < 0.001 and p < 0.005) and combination group (p < 0.001 and p < 0.05), but there was no significant difference in PR between pre-EGD (5 min after sitting on the sofa) and 5 min after the end of EGD, and PR at pre-EGD (15 min after sitting on the sofa) was significantly lower than pre-EGD (5 min after sitting on the sofa) in visual group (p < 0.005) and combination group (p < 0.001). Figure 3 shows the changes in BP from pre-EGD to post-EGD in the 4 groups. BPs during the early and the latter half of EGD, and 5 min after the end of EGD were significantly higher than pre-EGD (5 min after sitting on the sofa) in control group (p < 0.001, p < 0.05, and p < 0.05). BP during the early half of EGD was significantly higher than pre-EGD (5 min after sitting on the sofa) in the 3 distraction groups (p < 0.001), but no significant BP elevation was observed during the latter half of EGD and 5 min after the end of EGD. BP at pre-EGD (15 min after sitting on the sofa) was significantly lower than pre-EGD (5 min after sitting on the sofa) in the 3 distraction groups (p < 0.05). Fig. 4 shows the changes in SpO 2 from pre-EGD to post-EGD in the 4 groups. SpO 2 during the latter half of EGD was significantly higher than pre-EGD (5 min after sitting on the sofa) in control group, audio group, and visual group (p < 0.01, p < 0.005, and p < 0.005). Table 2 shows a comparison of PR at each point among the 4 groups. There was no significant difference in PR at pre-EGD (5 min after sitting on the sofa), during the early half of EGD, and the latter half of EGD among the 4 groups. However, there was a significant difference in PR at pre-EGD (15 min after sitting on the sofa) and 5 min after the end of EGD among the 4 groups on the Kruskal Wallis test (p < 0.001 and p < 0.01). Post-hoc pairwise comparisons revealed that PRs at pre-EGD (15 min after sitting on the sofa) and 5 min after the end of EGD in the 3 distraction groups were significantly lower than control group.

Comparison of PR at each point
Comparison of BP at each point Table 3 shows a comparison of BP at each point among the 4 groups. There was no significant difference in BP at pre-EGD (5 min after sitting on the sofa), during the early half of EGD, and the latter half of EGD among the 4 groups. However, there was a significant difference in BP at pre-EGD (15 min after sitting on the sofa) and 5 min after the end of EGD among the 4 groups on the Kruskal Wallis test (p < 0.005 and p < 0.05). Post-hoc pairwise comparisons revealed that BP at pre-EGD (15 min after sitting on the sofa) and 5 min after the end of EGD in visual group was significantly lower than control group. Table 4 shows a comparison of SpO 2 at each point among the 4 groups. There was no significant difference in SpO 2 at pre-EGD (5 min after sitting on the sofa), pre-EGD (15 min after sitting on the sofa), during the early half of EGD, and the latter half of EGD among the 4 groups. However, there was a significant difference in SpO 2 at 5 min after the end of EGD among the 4 groups on the Kruskal Wallis test (p < 0.01). Post-hoc pairwise comparisons revealed that SpO 2 at 5 min after the end of EGD in combination group were significantly higher than control group. Figure 5-A shows a comparison of Log HF power from pre-EGD to post-EGD among the 4 groups. There was a significant difference in Log HF power during the early and the latter half of EGD, and 5 min after the end of EGD among the 4 groups on the Kruskal Wallis test (p < 0.001, p < 0.01, and p < 0.05). Post-hoc pairwise comparisons revealed that Log HF powers during the early half of EGD in the 3 distraction groups was significantly higher than control group.  Figure 5-B shows a comparison of LF power/ HF power from pre-EGD to post-EGD between the 4 groups. There was a significant difference in LF power/ HF power at pre-EGD (15 min after sitting on the sofa) and 5 min after the end of EGD among the 4 groups on the Kruskal Wallis test (p < 0.001 and p < 0.001). Posthoc pairwise comparisons revealed that LF power/ HF power at pre-EGD (15 min after sitting on the sofa) and 5 min after the end of EGD in the 3 distraction groups was significantly lower than control group. Table 5 shows a comparison of POMS and the impression for EGD between pre-and post-distraction in the 3 distraction groups. The score for negative mood at postdistraction was significantly lower than at pre-distraction in the 3 distraction groups (p < 0.05). The VAS scores of strain, anxiety, and fear for EGD at post-distraction were significantly lower than pre-distraction in audio group (p < 0.05, p < 0.05, and NS), visual group (p < 0.005, NS, and NS), and combination group (p < 0.001, p < 0.05, and p < 0.05). Table 6 shows a comparison of the acceptance of the distraction after EGD among the 3 distraction groups.

Acceptance of distraction after EGD
There was a significant difference in usefulness of the distraction and satisfaction of the distraction among the 3 groups on the Kruskal Wallis test (p < 0.005). Posthoc pairwise comparisons revealed that the usefulness of the distraction and the satisfaction of the distraction in combination group was significantly higher than visual group. Although there was no significant difference in willingness for the next use of the distraction among the 3 groups, the degree of willingness for the next use of the distraction was excellent because the VAS was more than 70 in the 3 groups.

Discussion
Several studies examined the benefits of audio and video distraction during various endoscopy procedures   [1,[14][15][16][25][26][27][28][29][30][31]. However, no clear recommendations for distraction were established because assessments in previous reports were based solely on subjective items, such as tolerance, pain, anxiety and satisfaction. To our knowledge, this is the first study evaluating the influence of distractions on EGD using subjective and objective measures. The incidence of gastric cancer decreased worldwide in recent decades, but it remains a major cause of cancerrelated mortality [32]. Therefore, EGD is an indispensable instrument to discover upper gastrointestinal cancer and perform endoscopic treatments, such as EMR and ESD. Appropriate methods for amount and use of sedation, improved techniques and apparatus for endoscopy were established. However, serious complications related to endoscopic procedures and sedation remain and are a problematic. The exact mechanisms of these complications remain conjectural, but the importance of vital sign changes and causes related to the autonomic nerve system were demonstrated. There were several reports of an association with endoscopy procedure and the autonomic nervous system, but few reports associated EGD and distractions using objective assessments, such as vital signs and autonomic nervous function [33,34].
The present study demonstrated that BP at postdistraction (i.e., immediately pre-EGD) in the distraction groups improved significantly, but no improvement in BP was observed in the no distraction group. BP during and post-EGD increased significantly in the no distraction group, but no significant BP elevation was observed during the latter half of EGD and post-EGD in the distraction groups. There was also no significant elevation in PR at post-EGD in visual group, and combination group. These results suggest that distraction suppresses vital sign elevation at pre-EGD, during a portion of EGD, and at post-EGD.
There was a significant difference in Log HF power during the early half of EGD between the control group and distraction groups. The vomiting reflex affects the early half of EGD because of endoscope insertion. Additionally, gastrointestinal distention by air supply from the top of endoscopy may induce activation of a vagal reflex [35,36]. Promotion of parasympathetic nervous activity may be induced by not only the influence of distraction but also vomiting reflex and gastrointestinal distention because of stimulation of endoscope insertion.
The LF power/HF power ratios at post-distraction (i.e., immediately pre-EGD) and post-EGD in the distraction groups were significantly lower than control group. These results suggest that distraction inhibited activity of sympathetic nervous function.
The psychological influence of music or visual distraction on endoscopy procedures remains controversial, but the number of articles reporting positive effects on anxiety levels appears slightly greater than negative effects articles [1, 14-16, 25-31, 37]. The present study demonstrated that the scores for negative mood based on POMS and impression of EGD at post-distraction (immediately pre-EGD) improved significantly compared to the baseline condition in the distraction groups. Acceptance of distraction in all distraction groups was relatively good.
The present study had some limitations that should be noted. First, we used healing music and natural images that were selected as good by 20 volunteers in a premeeting for the selection of music prior to the start of the present study. However, whether the music and images used in this study were the more suitable for each subject is not clear. Second, different results may occur between persons who underwent EGD for the first time and persons who experienced EGD previously. Further investigation of subjects who undergo EGD for the first time or comparisons between persons who undergo EGD for the first time and repeated procedures is required. Last, there was a possibility of selection bias because all of the participants in the present study were healthy individuals undergoing a medical check-up. The mean of age of the subjects was relatively young. Whether sick persons or elderly populations would produce similar results to the present study is not clear. Further studies are necessary to resolve these limitations.